63 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Advanced Cell Classifier: User-Friendly Machine-Learning-Based Software for Discovering Phenotypes in High-Content Imaging Data.

Cell Syst. 2017 Jun 16;:

Authors: Piccinini F, Balassa T, Szkalisity A, Molnar C, Paavolainen L, Kujala K, Buzas K, Sarazova M, Pietiainen V, Kutay U, Smith K, Horvath P

Abstract
High-content, imaging-based screens now routinely generate data on a scale that precludes manual verification and interrogation. Software applying machine learning has become an essential tool to automate analysis, but these methods require annotated examples to learn from. Efficiently exploring large datasets to find relevant examples remains a challenging bottleneck. Here, we present Advanced Cell Classifier (ACC), a graphical software package for phenotypic analysis that addresses these difficulties. ACC applies machine-learning and image-analysis methods to high-content data generated by large-scale, cell-based experiments. It features methods to mine microscopic image data, discover new phenotypes, and improve recognition performance. We demonstrate that these features substantially expedite the training process, successfully uncover rare phenotypes, and improve the accuracy of the analysis. ACC is extensively documented, designed to be user-friendly for researchers without machine-learning expertise, and distributed as a free open-source tool at www.cellclassifier.org.

PMID: 28647475 [PubMed - as supplied by publisher]

A first report of rare earth elements in northwestern Mediterranean seaweeds.

Mar Pollut Bull. 2017 Jun 21;:

Authors: Squadrone S, Brizio P, Battuello M, Nurra N, Sartor RM, Benedetto A, Pessani D, Abete MC

Abstract
The concentrations of rare earth elements (REE) were determined by ICP-MS in dominant seaweed species, collected from three locations of the northwestern Mediterranean Sea. This is the first study to define levels and patterns of REE in macro algae from these coastal areas. Rare elements are becoming emerging inorganic contaminants in marine ecosystems, due to their worldwide increasing applications in industry, technology, medicine and agriculture. Significant inter-site and interspecies differences were registered, with higher levels of REE in brown and green macro algae than in red seaweeds. Levels of light REE were also observed to be greater compared to heavy REE in all samples. One of the investigated locations (Bergeggi, SV) had higher REE and ΣREE concentrations, probably due to its proximity to an important commercial and touristic harbor, while the other two sites were less affected by anthropogenic contaminations, and showed comparable REE patterns and lower concentrations.
CAPSULE: Rare earth elements in seaweeds.

PMID: 28647152 [PubMed - as supplied by publisher]

CRISPR/Cas9-mediated genome editing via postnatal administration of AAV vector cures haemophilia B mice.

Sci Rep. 2017 Jun 23;7(1):4159

Authors: Ohmori T, Nagao Y, Mizukami H, Sakata A, Muramatsu SI, Ozawa K, Tominaga SI, Hanazono Y, Nishimura S, Nureki O, Sakata Y

Abstract
Haemophilia B, a congenital haemorrhagic disease caused by mutations in coagulation factor IX gene (F9), is considered an appropriate target for genome editing technology. Here, we describe treatment strategies for haemophilia B mice using the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system. Administration of adeno-associated virus (AAV) 8 vector harbouring Staphylococcus aureus Cas9 (SaCas9) and single guide RNA (sgRNA) to wild-type adult mice induced a double-strand break (DSB) at the target site of F9 in hepatocytes, sufficiently developing haemophilia B. Mutation-specific gene editing by simultaneous induction of homology-directed repair (HDR) sufficiently increased FIX levels to correct the disease phenotype. Insertion of F9 cDNA into the intron more efficiently restored haemostasis via both processes of non-homologous end-joining (NHEJ) and HDR following DSB. Notably, these therapies also cured neonate mice with haemophilia, which cannot be achieved with conventional gene therapy with AAV vector. Ongoing haemophilia therapy targeting the antithrombin gene with antisense oligonucleotide could be replaced by SaCas9/sgRNA-expressing AAV8 vector. Our results suggest that CRISPR/Cas9-mediated genome editing using an AAV8 vector provides a flexible approach to induce DSB at target genes in hepatocytes and could be a good strategy for haemophilia gene therapy.

PMID: 28646206 [PubMed - in process]

Dacomitinib, a pan-inhibitor of ErbB receptors, suppresses growth and invasive capacity of chemoresistant ovarian carcinoma cells.

Sci Rep. 2017 Jun 23;7(1):4204

Authors: Momeny M, Zarrinrad G, Moghaddaskho F, Poursheikhani A, Sankanian G, Zaghal A, Mirshahvaladi S, Esmaeili F, Eyvani H, Barghi F, Sabourinejad Z, Alishahi Z, Yousefi H, Ghasemi R, Dardaei L, Bashash D, Chahardouli B, Dehpour AR, Tavakkoly-Bazzaz J, Alimoghaddam K, Ghavamzadeh A, Ghaffari SH

Abstract
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC. In this report, we show that dacomitinib, a pan-ErbB receptor inhibitor, diminished growth, clonogenic potential, anoikis resistance and induced apoptotic cell death in therapy-resistant EOC cells. Dacominitib inhibited PLK1-FOXM1 signalling pathway and its down-stream targets Aurora kinase B and survivin. Moreover, dacomitinib attenuated migration and invasion of the EOC cells and reduced expression of epithelial-to-mesenchymal transition (EMT) markers ZEB1, ZEB2 and CDH2 (which encodes N-cadherin). Conversely, the anti-tumour activity of single-targeted ErbB agents including cetuximab (a ligand-blocking anti-EGFR mAb), transtuzumab (anti-HER2 mAb), H3.105.5 (anti-HER3 mAb) and erlotinib (EGFR small-molecule tyrosine kinase inhibitor) were marginal. Our results provide a rationale for further investigation on the therapeutic potential of dacomitinib in treatment of the chemoresistant EOC.

PMID: 28646172 [PubMed - in process]

CRISPR-Cas12a-assisted recombineering in bacteria.

Appl Environ Microbiol. 2017 Jun 23;:

Authors: Yan MY, Yan HQ, Ren GX, Zhao JP, Guo XP, Sun YC

Abstract
Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a (Cpf1) has emerged as an effective genome editing tool in many organisms. Here, we developed and optimized a CRISPR-Cas12a assisted recombineering system to facilitate genetic manipulation in bacteria. Using this system, point mutations, deletions, insertions, and gene replacements can be easily generated on the chromosome or native plasmids in Escherichia coli, Yersinia pestis, and Mycobacterium smegmatis Because CRISPR-Cas12a-assisted recombineering does not require introduction of an antibiotic resistance gene into the chromosome to select for recombinants, it is an efficient approach for generating markerless and scarless mutations in bacteria.IMPORTANCE The CRISPR-Cas9 system has been widely used to facilitate genome editing in many bacteria. CRISPR-Cas12a (Cpf1), a new type of CRISPR-cas system, allows efficient genome editing in bacteria when combined with recombineering. Cas12a and Cas9 recognize different target sites, which allows for more precise selection of the cleavage target and introduction of the desired mutation. In addition, CRISPR-Cas12a assisted recombineering can be used for genetic manipulation of plasmids and plasmid curing. Finally, Cas12a-assisted recombineering in generating of point mutation, deletion, insertion and replacement in bacteria has been systematically analyzed. Taken together, our findings will guide efficient Cas12a-mediated genome editing in bacteria.

PMID: 28646112 [PubMed - as supplied by publisher]

MCAM mediates chemoresistance in small cell lung cancer via the PI3K/AKT/SOX2 signaling pathway.

Cancer Res. 2017 Jun 23;:

Authors: Tripathi SC, Fahrmann JF, Celiktas M, Aguilar M, Marini KD, Jolly MK, Katayama H, Wang H, Murage EN, Dennison JB, Watkins DN, Levine H, Ostrin EJ, Taguchi A, Hanash SM

Abstract
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors. MCAM depletion in chemoresistant cells reduced cell proliferation and reduced the IC50 inhibitory concentration of chemotherapeutic drugs in vitro. This MCAM-mediated sensitization to chemotherapy occurred via SOX2-dependent upregulation of mitochondrial 37S ribosomal protein 1/ATP binding cassette subfamily C member 1 (MRP1/ABCC1) and the PI3/AKT pathway. Metabolomic profiling revealed that MCAM modulated lactate production in chemoresistant cells that exhibit a distinct metabolic phenotype characterized by low oxidative phosphorylation. Our results suggest that MCAM may serve as a novel therapeutic target to overcome chemoresistance in SCLC.

PMID: 28646020 [PubMed - as supplied by publisher]

A rapid and quantitative method to detect human circulating tumor cells in a preclinical animal model.

BMC Cancer. 2017 Jun 23;17(1):440

Authors: Tu SH, Hsieh YC, Huang LC, Lin CY, Hsu KW, Hsieh WS, Chi WM, Lee CH

Abstract
BACKGROUND: As cancer metastasis is the deadliest aspect of cancer, causing 90% of human deaths, evaluating the molecular mechanisms underlying this process is the major interest to those in the drug development field. Both therapeutic target identification and proof-of-concept experimentation in anti-cancer drug development require appropriate animal models, such as xenograft tumor transplantation in transgenic and knockout mice. In the progression of cancer metastasis, circulating tumor cells (CTCs) are the most critical factor in determining the prognosis of cancer patients. Several studies have demonstrated that measuring CTC-specific markers in a clinical setting (e.g., flow cytometry) can provide a current status of cancer development in patients. However, this useful technique has rarely been applied in the real-time monitoring of CTCs in preclinical animal models.
METHODS: In this study, we designed a rapid and reliable detection method by combining a bioluminescent in vivo imaging system (IVIS) and quantitative polymerase chain reaction (QPCR)-based analysis to measure CTCs in animal blood. Using the IVIS Spectrum CT System with 3D-imaging on orthotropic-developed breast-tumor-bearing mice.
RESULTS: In this manuscript, we established a quick and reliable method for measuring CTCs in a preclinical animal mode. The key to this technique is the use of specific human and mouse GUS primers on DNA/RNA of mouse peripheral blood under an absolute qPCR system. First, the high sensitivity of cancer cell detection on IVIS was presented by measuring the luciferase carried MDA-MB-231 cells from 5 to 5x10(11) cell numbers with great correlation (R(2) = 0.999). Next, the MDA-MB-231 cell numbers injected by tail vein and their IVIS radiance signals were strongly corrected with qPCR-calculated copy numbers (R(2) > 0.99). Furthermore, by applying an orthotropic implantation animal model, we successfully distinguished xenograft tumor-bearing mice and control mice with a significant difference (p < 0.001), whereas IVIS Spectrum-CT 3D-visualization showed that blood of mice with lung metastasis contained more than twice the CTC numbers than ordinary tumor-bearing mice. We demonstrated a positive correlation between lung metastasis status and CTC numbers in peripheral mouse blood.
CONCLUSION: Collectively, the techniques developed for this study resulted in the integration of CTC assessments into preclinical models both in vivo and ex vivo, which will facilitate translational targeted therapy in clinical practice.

PMID: 28645267 [PubMed - in process]

Molecular cloning, structure, phylogeny and expression analysis of the invertase gene family in sugarcane.

BMC Plant Biol. 2017 Jun 23;17(1):109

Authors: Wang L, Zheng Y, Ding S, Zhang Q, Chen Y, Zhang J

Abstract
BACKGROUND: Invertases (INVs) are key enzymes regulating sucrose metabolism and are here revealed to be involved in responses to environmental stress in plants. To date, individual members of the invertase gene family and their expression patterns are unknown in sugarcane due to its complex genome despite their significance in sucrose metabolism.
RESULTS: In this study, based on comparative genomics, eleven cDNA and twelve DNA sequences belonging to 14 non-redundant members of the invertase gene family were successfully cloned from sugarcane. A comprehensive analysis of the invertase gene family was carried out, including gene structures, phylogenetic relationships, functional domains, conserved motifs of proteins. The results revealed that the 14 invertase members from sugarcane could be clustered into three subfamilies, including 6 neutral/alkaline invertases (ShN/AINVs), and 8 acid invertases (ShAINVs). Faster divergence occurred in acid INVs than in neutral/alkaline INVs after the split of sugarcane and sorghum. At least a one-time gene duplication event was observed to have occurred in the four groups of acid INVs, whereas ShN/AINV1 and ShN/AINV2 in the β8 lineage were revealed to be the most recently duplicated genes among their paralogous genes in the β group of N/AINVs. Furthermore, comprehensive expression analysis of these genes was performed in sugarcane seedlings subjected to five abiotic stresses (drought, low temperature, glucose, fructose, and sucrose) using Quantitative Real-time PCR. The results suggested a functional divergence of INVs and their potential role in response to the five different treatments. Enzymatic activity in sugarcane seedlings was detected under five abiotic stresses treatments, and showed that the activities of all INVs were significantly inhibited in response to five different abiotic stresses, and that the neutral/alkaline INVs played a more prominent role in abiotic stresses than the acid INVs.
CONCLUSIONS: In this study, we determined the INV gene family members of sugarcane by PCR cloning using sorghum as a reference, providing the first study of the INV gene family in sugarcane. Combining existing INV gene data from 7 plants with a comparative approach including a series of comprehensive analyses to isolate and identify INV gene family members proved to be highly successful. Moreover, the expression levels of INV genes and the variation of enzymatic activities associated with drought, low temperature, glucose, fructose, and sucrose are reported in sugarcane for the first time. The results offered useful foundation and framework for future research for understanding the physiological roles of INVs for sucrose accumulation in sugarcane.

PMID: 28645264 [PubMed - in process]

Spatially resolved metabolic analysis reveals a central role for transcriptional control in carbon allocation to wood.

J Exp Bot. 2017 Jun 22;:

Authors: Roach M, Arrivault S, Mahboubi A, Krohn N, Sulpice R, Stitt M, Niittylä T

Abstract
The contribution of transcriptional and post-transcriptional regulation to modifying carbon allocation to developing wood of trees is not well defined. To clarify the role of transcriptional regulation, the enzyme activity patterns of eight central primary metabolism enzymes across phloem, cambium, and developing wood of aspen (Populus tremula L.) were compared with transcript levels obtained by RNA sequencing of sequential stem sections from the same trees. Enzymes were selected on the basis of their importance in sugar metabolism and in linking primary metabolism to lignin biosynthesis. Existing enzyme assays were adapted to allow measurements from ~1 mm3 sections of dissected stem tissue. These experiments provided high spatial resolution of enzyme activity changes across different stages of wood development, and identified the gene transcripts probably responsible for these changes. In most cases, there was a clear positive relationship between transcripts and enzyme activity. During secondary cell wall formation, the increases in transcript levels and enzyme activities also matched with increased levels of glucose, fructose, hexose phosphates, and UDP-glucose, emphasizing an important role for transcriptional regulation in carbon allocation to developing aspen wood. These observations corroborate the efforts to increase carbon allocation to wood by engineering gene regulatory networks.

PMID: 28645173 [PubMed - as supplied by publisher]

Genomic Characterization of Two Novel SAR11 Isolates From the Red Sea, Including the First Strain of the SAR11 Ib clade.

FEMS Microbiol Ecol. 2017 Jun 22;:

Authors: Jimenez-Infante F, Ngugi DK, Vinu M, Blom J, Alam I, Bajic VB, Stingl U

Abstract
The SAR11 clade (Pelagibacterales) is a diverse group that forms a monophyletic clade within the Alphaproteobacteria, and constitutes up to one third of all prokaryotic cells in the photic zone of most oceans. Pelagibacterales are very abundant in the warm and highly saline surface waters of the Red Sea, raising the question of adaptive traits of SAR11 populations in this water body and warmer oceans through the world. In this study, two pure cultures were successfully obtained from surface waters on the Red Sea, one isolate of subgroup Ia and one of the previously uncultured SAR11 Ib lineage. The novel genomes were very similar to each other and to genomes of isolates of SAR11 subgroup Ia (Ia pan-genome), both in terms of gene content and synteny. Among the genes that were not present in the Ia pan-genome, 108 (RS39, Ia) and 151 genes (RS40, Ib) were strain-specific. Detailed analyses showed that only 51 (RS39, Ia) and 55 (RS40, Ib) of these strain-specific genes had not reported before on genome fragments of Pelagibacterales. Further analyses revealed the potential production of phosphonates by some SAR11 members and possible adaptations for oligotrophic life, including pentose sugar utilization and adhesion to marine particulate matter.

PMID: 28645159 [PubMed - as supplied by publisher]

67 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/24

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

44 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/22

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

46 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

54 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward?

Mol Diagn Ther. 2017 Jun 17;:

Authors: Langley RJ, Wong HR

Abstract
Sepsis remains one of the leading causes of death in the USA and it is expected to get worse as the population ages. Moreover, the standard of care, which recommends aggressive treatment with appropriate antibiotics, has led to an increase in multiple drug-resistant organisms. There is a dire need for the development of new antibiotics, improved antibiotic stewardship, and therapies that treat the host response. Development of new sepsis therapeutics has been a disappointment as no drugs are currently approved to treat the various complications from sepsis. Much of the failure has been blamed on animal models that do not accurately reflect the course of the disease. However, recent improvements in metabolomic, transcriptomic, genomic, and proteomic platforms have allowed for a broad-spectrum look at molecular changes in the host response using clinical samples. Integration of these multi-omic datasets allows researchers to perform systems biology approaches to identify novel pathophysiology of the disease. In this review, we highlight what is currently known about sepsis and how integrative omics has identified new diagnostic and predictive models of sepsis as well as novel mechanisms. These changes may improve patient care as well as guide future preclinical analysis of sepsis.

PMID: 28624903 [PubMed - as supplied by publisher]

High-throughput screening technologies for enzyme engineering.

Curr Opin Biotechnol. 2017 Jun 15;48:196-202

Authors: Longwell CK, Labanieh L, Cochran JR

Abstract
Emerging technologies are enabling ultra-high-throughput screening of combinatorial enzyme libraries to identify variants with improved properties such as increased activity, altered substrate specificity, and increased stability. Each of these enzyme engineering platforms relies on compartmentalization of reaction components, similar to microtiter plate-based assays which have been commonly used for testing the activity of enzyme variants. The technologies can be broadly divided into three categories according to their spatial segregation strategy: (1) cells as reaction compartments, (2) in vitro compartmentalization via synthetic droplets, and (3) microchambers. Here, we discuss these emerging platforms, which in some cases enable the screening of greater than 10 million enzyme variants, and highlight benefits and limitations of each technology.

PMID: 28624724 [PubMed - as supplied by publisher]

Drought responsive microRNAs in two barley cultivars differing in their level of sensitivity to drought stress.

Plant Physiol Biochem. 2017 Jun 07;118:121-129

Authors: Fard EM, Bakhshi B, Keshavarznia R, Nikpay N, Shahbazi M, Salekdeh GH

Abstract
MicroRNAs (miRNAs) are known to be involved in the regulation of gene expression, including that of genes involved in the response to stress. Here, a comparison has been drawn between the miRNA profiles of a drought susceptible, 'Morocco 9-75', and a drought tolerant, 'Yousef', barley cultivars. Leaf water content, shoot dry matter and chlorophyll content decreased in 'Morocco 9-75' more considerably compared with 'Yousef' under drought stress. Furthermore, lower stomatal conductance and higher leaf temperature were observed in 'Morocco 9-75' compared with 'Yousef'. Based on the criteria set for differential abundance, 118 of conserved and novel miRNAs were identified as being responsive to soil water status. Although drought stress resulted in an altered abundance of more miRNAs in 'Morocco 9-75' than in 'Yousef', drought stress was generally associated with an increased miRNA abundance in 'Yousef' and a decreased abundance in 'Morocco 9-75'. An in silico analysis identified 645 genes as putative targets for the drought-responsive miRNAs in 'Yousef' and 3735 in 'Morocco 9-75'. Gene ontology analysis showed that drought stress was associated with the altered abundance of miRNAs targeting growth, development, the juvenile to adult transition and hormone signaling. Some miRNAs which became more abundant in 'Yousef' are thought to target genes intimately involved in development and stress adaptation. In 'Morocco 9-75', drought stress induced changes in the abundance of miRNAs associated with genes affecting growth, development, the juvenile to adult transition and ABA signaling. The data imply that miRNAs may affect the tolerance/sensitivity of barley to drought stress by modulating the expression of a wide set of genes and induction of some physiological changes.

PMID: 28624683 [PubMed - as supplied by publisher]

Alternative Polyadenylation Patterns for Novel Gene Discovery and Classification in Cancer.

Neoplasia. 2017 Jun 15;19(7):574-582

Authors: Begik O, Oyken M, Cinkilli Alican T, Can T, Erson-Bensan AE

Abstract
Certain aspects of diagnosis, prognosis, and treatment of cancer patients are still important challenges to be addressed. Therefore, we propose a pipeline to uncover patterns of alternative polyadenylation (APA), a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we analyzed expression data for 1045 cancer patients and found a significant shift in usage of poly(A) signals in common tumor types (breast, colon, lung, prostate, gastric, and ovarian) compared to normal tissues. Using machine-learning techniques, we further defined specific subsets of APA events to efficiently classify cancer types. Furthermore, APA patterns were associated with altered protein levels in patients, revealed by antibody-based profiling data, suggesting functional significance. Overall, our study offers a computational approach for use of APA in novel gene discovery and classification in common tumor types, with important implications in basic research, biomarker discovery, and precision medicine approaches.

PMID: 28624626 [PubMed - as supplied by publisher]

Cell-Size-Dependent Transcription of FLC and Its Antisense Long Non-coding RNA COOLAIR Explain Cell-to-Cell Expression Variation.

Cell Syst. 2017 Jun 08;:

Authors: Ietswaart R, Rosa S, Wu Z, Dean C, Howard M

Abstract
Single-cell quantification of transcription kinetics and variability promotes a mechanistic understanding of gene regulation. Here, using single-molecule RNA fluorescence in situ hybridization and mathematical modeling, we dissect cellular RNA dynamics for Arabidopsis FLOWERING LOCUS C (FLC). FLC expression quantitatively determines flowering time and is regulated by antisense (COOLAIR) transcription. In cells without observable COOLAIR expression, we quantify FLC transcription initiation, elongation, intron processing, and lariat degradation, as well as mRNA release from the locus and degradation. In these heterogeneously sized cells, FLC mRNA number increases linearly with cell size, resulting in a large cell-to-cell variability in transcript level. This variation is accounted for by cell-size-dependent, Poissonian FLC mRNA production, but not by large transcriptional bursts. In COOLAIR-expressing cells, however, antisense transcription increases with cell size and contributes to FLC transcription decreasing with cell size. Our analysis therefore reveals an unexpected role for antisense transcription in modulating the scaling of transcription with cell size.

PMID: 28624615 [PubMed - as supplied by publisher]